From The Editor | February 26, 2021

Keeping Clinicals On-Pace In The COVID-19 Age


By Matthew Pillar, Editor, BioProcess Online

Laser Surgery

Lineage Cell Therapeutics CEO Brian Culley is inspired by the speed and agility at which the biopharma industry—including the FDA—are working to get new cell therapies to market, despite the clinical disruptions of the day.

With three cellular therapies designed to address three distinct diseases in the clinic, Lineage Cell Therapeutics is up to its elbows in regulatory interface. Its OpRegen candidate is being evaluated in a Phase 1/2a open-label, dose escalation safety and efficacy study of human retinal pigment epithelium cells transplanted subretinally in patients with advanced dry AMD with geographic atrophy. OPC, the company’s oligodendrocyte progenitor cell therapy candidate, is in a Phase 1/2a trial for acute spinal cord injuries. Just beginning the clinical journey is VAC2, an allogeneic cancer vaccine candidate designed to stimulate patient immune responses to telomerase, which is commonly expressed in cancerous cells.  On episode 30 of the Business of Biotech podcast, CEO Brian Culley tells us the pace of his company’s interaction with the FDA has been brisk, as has the creative energy the company is putting into keeping clinical trials moving forward during the COVID-19 pandemic.

Will Unprecedented Regulatory Speed Continue?

The rush to address COVID-19 has given biopharma and the FDA a very public proving ground to push the barriers of time. “What we're seeing at the regulatory level is certainly unprecedented,” says Culley. “It’s marked by abundant speed and flexibility, and for great reason. We've got thousands of people dying every moment.” That speed has established a new precedent for agile processes, policies, and procedures in near real-time, though it remains to be seen whether the precedent will last. “Whether that trickles down and establishes long-term policies and procedures and habits in the Agency’s interaction with sponsors is hard to say,” says Culley, “because much of this is attributable to COVID, and COVID is, thankfully, temporary. Drug development is not temporary. I think we're going to see some aspects of this parallel universe that we're working in that that will be carried over, because the parallel universe has shown what’s possible. But there are trade-offs, so we’ll most likely end up somewhere in the middle when everything is settled and back to some degree of normalcy.”

Brian Culley, CEO, Lineage Cell Therapeutics

Cully cautions that, while the pandemic has clearly brought the importance of having tools and processes to deal with infectious diseases into focus, attention spans in a fast-moving business are fickle. When we’re on the other side of the pandemic, he says, society will have benefitted. “There’s more attention on the field, more government and private sector support. When there's a problem, you've got all these entrepreneurial minds thinking about solutions, from on new ideas to speed genetic sequencing and drug discovery to shipping and handling and logistics. But pandemics are rare. Maybe a hundred years from now if there hasn't been another massive one, we’ll be caught on our heels. The capitalistic environment that we're in is going to move on to other things.”

As it relates to resources and speed, Culley anticipates the momentum will trickle into fields beyond those working explicitly on COVID-19 therapeutics and vaccines. “Everything is COVID right now, so if you happen to be working in that area, you have more privileges and opportunities than companies in other spaces. Now that we’re seeing some light at the end of the tunnel, I think we’ll see some return to a more balanced engagement.” For now, Culley says COVID-19 gets you to the front of the line. “In the current environment, a company like Lineage would not have been able to have a phone call with representatives from BARDA and the NIH and the FDA all at once were the conversation not centered on COVID-19,” he says. “Companies that are working in urgent areas like the pandemic have an opportunity to cut to the front of the line, and they deserve that breathing room. There’s something quite important happening. As we return to normal, those of us in spaces like cell and gene therapy will have to make sure we’re borrowing best practices from the regulatory work being done in the infectious disease space and apply those practices moving forward.”

Ensuring Momentum Isn’t Stifled In The Clinic

The OpRegen program is the lead candidate at Lineage, and its clinical trials faced serious risk from the outset of the pandemic. Dry age-related macular degeneration is a condition that impacts the elderly—the population of people that are most susceptible to COVID-19. Clinical participation is elective. That’s an equation that simply invites trial participants to opt out of travelling to the clinic for their treatment. “When you have people who are skipping their appointments, that allows their disease to progress, so the pandemic has been really bad for ophthalmology trials in general,” says Culley. Fortunately, the Lineage OpRegen trial is geographically dispersed. With trial sites in both the U.S. and Israel, the company was able to ramp up clinical operations in the U.S. when Israel was hardest hit, and visa versa.  When Culley joined the company in 2018, one of his first orders of business was to expand clinical trail sites in both countries. That proved a fortuitous move when the pandemic set in. Even within both countries, the company was able to throttle up clinical activity in geographies where COVID-19 was less pervasive and throttle down that activity in COVID-19 hotspots.

“We're working in a disease for which there is a long, slow measurement. This isn't like an acute infectious disease,” says Culley. “We're looking at changes that occur in the eye over about a year. If a trial participant is supposed to go in for a six- or nine-month assessment and they decide to skip or delay that assessment, we've unfortunately missed a data point, but it doesn't render that data meaningless.”

In at least one instance, the OpRegen clinical trial actually benefitted from a pandemic-related hiccup. While standard protocol is to suppress patients' immune response to help ensure the therapy isn't rejected, at least one patient in the study opted to forego immunosuppression due to the individual's line of work. Rather than bow out of the trial, the patient opted to continue with treatment without undergoing immunosuppression. This is allowing Lineage to collect data on the effects of its treatment in the presence of a healthy immune system.

When faced with adversity, says Culley, you have to adapt. “You can't just throw your hands up and say, ‘I'll wait.’ It's too expensive to wait.”

Listen in on episode 30 of the Business of Biotech to learn more about the steps Culley and Lineage Cell Therapeutics took to keep its clinical trials on the rails during the COVID-19 pandemic.